Chronic exposure of human to ultraviolet radiation (UVR) is known to cause photoaging (dermatoheliosis), non-melanoma skin cancer, and possibly melanoma. The specific aims of this project are directed to demonstrate the: a) molecular nature of photoaging and biochemical approaches for its amelioration; b) role of UVR in the induction of melanoma; c) usefulness of new and potent chemicals to stimulate melanin pigmentation of angelicins, khellin, and synthetic alpha-MSH melanotrophins; d) role of reactive 02 species in cutaneous phototoxic reactions by psoralens; and e) role of cutaneous involving the alterations of collagen, glycosaminoglycans, elastin, and certain enzymes in hairless mice subjected to photoaging by repeated exposure to UVB and UVA radiation. Studies involve determination of Type I and III collagen, cross-links and collagen, changes in 4-OH-prolyl-4'- hydroxylase, lysyl hydroxylase, desmosine, isodesmosine, and proteoglycans and evaluation of the role of certain free radical scavengers and antioxidants (e.g., beta-carotene, alpha-tocopherol, ethyl sorbate, B-alanyl-l-histidine) in the prevention of amelioration of biochemical alterations in photoaging. In Project II, the cause-effect relationship evidenced by epidemiological data on the development of melanoma by UVR, will be substantiated by animal experimentation and irradiation with UVB and UVA, crude action spectrum studies, and histologic confirmation in two animal models (black guinea pigs and pigmented hairless mice) by first producing blue nevi by topical DMBA treatment and subsequent repeated exposures to UVB and UVA of blue nevus-like pigmented macules. In Project III, the usefulness and the mode of melanin pigmentation by new nonphototoxic furocoumarins, furancohromones, and potent synthetic melanotrophins for the possible treatment of patients with vitiligo will be evaluated. Project IV includes studies to elucidate the role of reactive in the pathogenesis of phototoxic reaction induced by psoralens + UVA and involves the determination of prostaglandins in the presence and absence of selective quenchers of reactive 02 and free radicals. In Project V, the age-related changes of SOD in humans skin biopsies and cultured human keratinocytes will be studied to demonstrated the importance of mammalian skin SOD in photoaging.